Linked Life Data

2988566

Source:http://linkedlifedata.com/resource/pubmed/id/2988566

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
1985-7-10
pubmed:abstractText
Cyproterone acetate (CA) inhibited 1-24 ACTH (50 ng/l)-stimulated cortisol production by dispersed guinea-pig adrenal cells in a dose-related manner. Inhibition occurred over the range 10(-6) to 5 X 10(-5) moles/l. The concentration of drug which induced 50% inhibition was 4.6 X 10(-6) moles/l. The sites of action of this anti-steroidogenic effect have been established. Dispersed adrenal cells were challenged with the cortisol precursor steroids (all at 10(-5) moles/l) pregnenolone (Pe), 17 alpha hydroxypregnenolone (17-OH Pe), 17 alpha-hydroxyprogesterone (17-Po), and 11 deoxycortisol or 1-24 ACTH (100 ng/1) in the absence and presence of increasing concentrations of CA (10(-5) to 10(-4) moles/l). In the absence of drug, the steroid precursors or ACTH provoked cortisol secretion greater than 10-fold that secreted by cells incubated in their absence. ACTH-stimulated cortisol secretion was inhibited greater than 68% at concentrations of CA greater than 10(-5) moles/l. CA (10(-5) moles/l) had no significant effect on steroid-stimulated cortisol production when the delta 4, 3 ketosteroids 17-OH Po and 11-deoxycortisol were used, but depressed secretion by greater than 61% (P less than 0.001) when the delta 5 3 beta hydroxysteroids (Pe, 17-OH Pe) were employed. Increasing CA concentrations to 10(-4) moles/l had little effect on cortisol secretion provoked by 11-deoxycortisol, but significantly (P less than 0.05) depressed cortisol secretion stimulated by 17-OH Po. These results suggest that the major site of action of CA is delta 5, 3 beta hydroxysteroid dehydrogenase (3 beta-HSD) with a secondary effect on 21-hydroxylase activity. To confirm these findings cortisol secretion provoked by 17, 21, dihydroxypregnenolone (17, 21 diOH Pe) and 21 deoxycortisol (21-DOC) was measured in the absence and presence of increasing concentrations of CA. At the lowest concentration of CA (5 X 10(-6) moles/l), cortisol secretion provoked by 17, 21 diOH Pe was inhibited by 28% (P less than 0.01) whereas secretion provoked by 21-DOC was not significantly affected. At the highest concentration of CA (10(-4) moles/l), the relative inhibition was 80% for 17, 21 diOH Pe and 38% for 21-DOC. We conclude that cyproterone acetate inhibits adrenal steroidogenesis at both 3 beta-HSD and 21-hydroxylase, the degree of inhibition being more pronounced at 3 beta-HSD.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0006-2952
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
34
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2091-5
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1985
pubmed:articleTitle
On the site of action of the anti-adrenal steroidogenic effect of cyproterone acetate.
pubmed:publicationType
Journal Article, In Vitro